Optic neuritis is a common cause of visual loss in young adults and is also often the first manifestation of multiple sclerosis. It has been found that about 75% of patients presenting with optic neuritis progress to clinically definite multiple sclerosis (CDMS) within 15 years. The ophthalmologists may thus be the first to consider a diagnosis of multiple sclerosis.
MS is an inflammatory autoimmune disease characterized by axon demyelination and loss. A significant proportion of MS patients initially present with optic neuritis (ON), which is characterized by optic nerve damage. Clinical studies, particularly from the Optic Neuritis Study Group (ONTT), have helped clarify the natural history and treatment of optic neuritis. These studies have shown that, compared with oral prednisolone or placebo, treatment with intravenous methylprednisolone (IVMP) results in more rapid recovery of vision but without long term difference in visual acuity, see e.g., current Opin Neurol. 1995 February; 8(1):72-6 for a description of the ONTT protocol and results, reproduced herein.
The ONTT was developed to answer the following questions: (1) Does treatment of optic neuritis with either oral or intravenous steroids reduce permanent optic nerve damage? (2) Does either treatment speed recovery? (3) Are the complications of steroid treatment insignificant in relation to the magnitude of the treatment effect? To be eligible for the study, patients must have the following characteristics: acute unilateral optic neuritis with visual symptoms of eight days' duration or less; age between 18 and 45 years; no previous history of optic neuritis or optic disc pallor in the involved eye; and a relative afferent pupillary defect and a visual field defect in the involved eye. Patients entering the study will be randomized to receive one of three treatment allocations: (1) oral prednisone (1 mg/kg/d for 14 days); (2) intravenous methylprednisolone sodium succinate (1000 mg/d for three days) followed by oral prednisone for 11 days; and 3 oral placebo for 14 days. There will be short tapering off of each oral regimen. Prednisone was selected because it is the treatment currently having the most widespread use. Intravenous methylprednisolone was selected because recent experience with its use in optic neuritis and multiple sclerosis has demonstrated potentially promising results. Outcome determinations will be made during the first month to assess rate of improvement and at six months to assess the degree of residual visual dysfunction. Contrast sensitivity measured with the Pelli-Robson hart (Foresight, Syracuse, N.Y.) and perimetry performed on both the Humphrey Field Analyzer (Allergan Humphrey, San Leandro, Calif.) and Goldmann perimeter will serve as the primary determinants of treatment effect. Visual acuity and color vision will also be assessed. Contrast sensitivity was chosen as a primary measure of outcome because it is abnormal in a high percentage of cases of resolved optic neuritis and correlates well with the patient's subjective complaints.
Thus, there remains a need to improve the current protocols for the treatment of optic neuritis.
Additional clinical studies have suggested the use of interferon-beta (IFN-beta) in the context of optic neuritis or the treatment of the 1st clinical event in ‘risk patients’ for clinically definite multiple sclerosis:
For example, Balcer and Galetta, Semin Opthalmol. 2002 March; 17(1):4-10, suggest the treatment of demyelinating optic neuritis in patients at high risk for developing clinically definite multiple sclerosis (CDMS) with methylpredinisolone i.v. (IVMP) followed by prednisone po and ifn-beta 1a at 30 microgram (mcg) i.m. 1× weekly or 22 mcg s.c. 1× weekly.
The CHAMPS study explored early use of ifn-beta at 30 mcg i.m. weekly to reduce the rate of conversion to CDMS after a 1st clinical event in ‘risk patients’ (MRI criteria: >2 T2-lesions) and ‘high risk patients’ (>9 T2-lesions, >1 gadolinium pos. lesion).
Similarly, the ETOMS study explored early use of ifn-beta at 22 mcg s.c. weekly to reduce the rate of conversion to CDMS after a 1st clinical event of risk patients (patient has >4 T2-lesions or 3 lesions one of which was infratentorial or gadolinium positive).
None of the currently available drug regimens for the treatment of optic neuritis is fully satisfactory. Accordingly, it is an object of the present invention to provide an improved treatment of optic neuritis.